CORE F ? PROJECT SUMMARY/ABSTRACT The Biomarker Core (Core F) of the ADRC will provide services, resources and expertise in the vascular, blood- brain barrier (BBB), neurovascular unit (NVU) and standard Alzheimer?s disease (AD) amyloid-? (A?) and tau biomarkers for USC ADRC and outside investigators. This will support the central theme of our ADRC to elucidate vascular contributions to cognitive impairment and AD, and the role of cerebrovascular system, vascular and metabolic risk factors (VMRF), and NVU in cognitive decline and the pathogenesis of dementia and AD. The Biomarker Core F has expertise in developing novel vascular, BBB and NVU cell- and system-specific biomarkers in biofluids in addition to AD biomarkers (e.g., A?, tau, pTau). Core F will determine simultaneously in the cerebrospinal fluid (CSF) and plasma in participants of the primary ADRC vascular cohort study (VCS) biomarkers of vascular and BBB injury, other NVU biomarkers (e.g., astrocytes, microglia, inflammatory response, and neuronal injury) and AD A?, tau, and pTau biomarkers. Core F will also conduct A? and tau measurements and APOE genotyping in all ADRC participants that consent to CSF and/or blood collection. Existing strengths of our core include i) decades of experience and knowledge in studying the BBB, cerebrovascular system, and NVU; ii) experience in developing novel vascular/BBB biomarkers, as for example new, sensitive assays for novel analytes of interest including sPDGFR? (pericyte injury marker), pleiotrophin (PTN, a growth factor expressed by brain capillary pericytes), cyclophilin A, ferritin, active TGF-?1, as well as A? and tau oligomer assays.; iii) providing reliable and simultaneous measurements of multiple NVU biomarkers in biofluids for all pilot data analyses of ADRC investigators using the ultrasensitive electrochemiluminescent Meso Scale Discovery (MSD) multiplex platform; and iv) on-going multi-year collaborations with several USC ADRC investigators including Drs. Chui, Toga, Harrington, Ringman, Wang, Nation, Yassine, Braskie, Pa, and others, and several external investigators working in the AD field (resulting in numerous publications). Core F will also generate and maintain a BioBank of peripheral blood mononuclear cells (PBMCs) to be sent and deposited to the NIH National Centralized Repository for Alzheimer?s Disease and Related Dementias (NCRAD), and of induced pluripotent stem cells (iPSC) for ADRC investigators? working on in vitro models of NVU, BBB and/or ?brain on a chip?. Under the leadership of Dr. Zlokovic and the resources available at USC Zilkha Neurogenetic Institute, Core F will 1) coordinate and standardize biofluid collection, processing, storage and distribution; 2) assay CSF and plasma for vascular, BBB, NVU and standard AD biomarkers and conduct APOE genotyping; 3) provide technological developments; 4) generate and maintain a BioBank of PBMCs and iPSCs; and 5) facilitate data management, requests, and distribution to USC ADRC investigators to support our ADRC?s scientific goals. .